The proposed research examines the influence of hydrodynamic cell-cell and cell-vessel wall interactions under physiological flow conditions on platelet adhesion dynamics at microscale resolution. The specific aims of this proposal are: 1. 3-D modeling of platelet adhesion with reactive surfaces under flow, and 2. Experimental and theoretical characterization of cell aggregation under flow. A recently developed rigorous numerical simulation called Multiparticle Adhesive Dynamics (MAD) models the adhesion of spherical cells to surfaces in any general flow field, and will be extended to simulate 3-D platelet (oblate spheroid) adhesive interactions with surface-bound von Willebrand factor in shear flow. The simulation will include cell-cell (RBC-platelet) hydrodynamic interactions as well as cell aggregation (neutrophil-platelet) separately. Flow experiments of platelet adhesion in solutions of varying hematocrit will be conducted to determine the influence of RBC-platelet collisions on platelet deposition rate. Cell aggregation between platelets and leukocytes near a surface in shear field will also be examined experimentally. This research aims to characterize the interplay between specific chemical adhesion and hydrodynamic forces.